Studies on indicator dispersion in the circulation and exchanges of solutes between blood and tissues are being approached with a variety of experimental techniques, with the emphasis being on exchanges of hydrophilic solutes and ions in the myocardium. Tracer extraction techniques are used for obtaining estimates of capillary permeability- surface products, and of mechanisms of endothelial permeation. Osmotic water exchanges are used for obtaining more refined estimates of the functional dimensions of clefts between endothelial cells, and of tissue stiffness and water permeablity. Tracers are used for studies on intramyocardial diffusion. Microsphere deposition is used for estimating flow heterogeneity, and tracers for heterogeneities of volumes of distribution and permeabilities. Filling of the microvasculature with silicon elastomer is used for making detailed measurements on microvascular arrangements. Methods are being evolved for relating intravascular dilution curves to signals obtained externally by gamma detectors. The studies should provide data on the mechanisms of substrate and metabolite exchange in the heart.